As men age, they experience many conditions, such as mobility disability, age-associated memory impairment, and low vitality, that result in decreased ability to perform activities of daily living, increased propensity to fall, and decreased independence. They also experience anemia, osteoporosis and metabolic syndrome and decreased sexual function. One cause that could contribute to all of these conditions is a low serum testosterone concentration. As men age, their serum testosterone falls, often to levels comparable to those of younger men who have diseases of the pituitary and testes. When young men develop low testosterone due to pituitary or testicular disease, they experience similar consequences, including decreased muscle mass and strength, decreased sexual drive, impaired cognition, and low energy, as well as anemia, osteoporosis and the metabolic syndrome. When these men are treated with testosterone, all of these abnormalities improve. The concept we propose is that an unequivocally low testosterone concentration for no apparent reason other than age predisposes a man to have these geriatric conditions and that testosterone treatment will improve them. We therefore propose a closely coordinated set of four, randomized, placebo-controlled clinical trials to test the hypotheses that testosterone treatment for one year of men >65 years who have unequivocally low serum testosterone concentrations (<250 ng/dL) and both symptoms and objective evidence of mobility disability, age-associated memory impairment, low vitality, or diminished sexual function will show more favorable changes in these parameters than placebo treatment. We shall select 1200 men at 18 sites and randomize them to receive testosterone or placebo gel for one year. Primary end points for these four trials will be six minute walking distance (mobility disability), paragraph recall by the Wechsler Memory Scale Revised (age-associated memory impairment), Facit-fatigue scale (vitality) and UCLA 7-day sexual function questionnaire (sexual function). Measures across all trials will include patient global assessment of change questions, activities of daily living, falls, PHQ-9 and Positive and Negative Affect scales, as well as assessment of adverse events, including prostate diseases. Subsets of men will be assessed for cardiovascular disease by electron beam CT;volumetric bone density of the spine by quantitative CT;and anemia. The potential significance of this study is that it should determine, finally, if testosterone treatment of older men with low testosterone concentrations will improve their physical, sexual and cognitive function and vitality. This study will also provide preliminary data that will help determine if a longer-term trial of the effects of testosterone on clinical heart disease, fracture risk and prostate risk is warranted.